Antiviral Development for the Polio Endgame: Current Progress and Future Directions

Abstract

As the world is approaching the eradication of wild poliovirus serotype 1, the last of the three wild types, the question of how to maintain a polio-free world becomes imminent. To mitigate the risk of sporadic vaccine-associated paralytic polio (VAPP) caused by oral polio vaccines (OPVs) that are routinely used in global immunization programs, the Polio Antivirals Initiative (PAI) was established in 2006. The primary goal of the PAI is to facilitate the discovery and development of antiviral drugs to stop the excretion of immunodeficiency-associated vaccine-derived poliovirus (iVDPV) in B cell-deficient individuals. This review summarizes the major progress that has been made in the development of safe and effective poliovirus antivirals and highlights the candidates that have shown promising results in vitro, in vivo, and in clinical trials.

Keywords: antiviral development; capsid-binding agent; immunodeficiency-associated vaccine-derived poliovirus; picornavirus; poliovirus; small molecule-based antiviral drug.

Figure 1

Poliovirus structure and viral genome and polyprotein organization. (a) Cryo-EM structure of poliovirus serotype 1 complexed with three domain CD155. Image from the RCSB PDB (RCSB.org) of PDB ID 1DGI [27]. (b) Schematic illustration of hydrophobic pocket in the viral capsid filled with pocket factor. (c) Organization of poliovirus genome and viral polyprotein processing (images in (b,c) were created with BioRender.com).